More than 90% of malignant gliomas are localized to one area of the brain, yet chemotherapy, developed for disseminated disease, has been the principal experimental thrust in their treatment. Most small, focal tumors are curable by surgery and radiation; and radiation is emerging as the most effective modality in the treatment of malignant gliomas, limited only by toxicity to normal brain. Local interstitial brachytherapy with its favorable therapeutic ratio is, therefore, a logical treatment technique for malignant brain tumors, and our experience is stereotactically delivering radioactive sources to these lesions has been favorable, particularly with removeable, high activity 125I. Because responses have been characteristically short-lived and many of these lesions grossly necrotic, we have treated some patients with hypoxic cell radiosensitizers during 125I implant therapy. The interactions of hypoxic cell radiosensitizers and radiation delivered at low dose rates are poorly understood; and no rodent model for interstitial brachytherapy exists, despite its potential advantages over externally delivered radiation for studying low dose rate radiation in vivo. We will develop a system for removable interstitial 125I implants in RIF-1 tumors in C3H mice and completely define its dosimetry and response to various radiation dose rates using the cell survival, regrowth delay, and local tumor control assays. With this as a basis, and using the same endpoints, we will study the interactions of low dose rate radiation with 2 promising classes of sensitizers, the nitroimidazoles (misonidazole, Ro 05-9963) and the platinum complexes (cis-dichlorodiammineplatinum (II)).